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排序方式: 共有83条查询结果,搜索用时 15 毫秒
61.
Thompson CF Quraishi N Ali A Mosley RT Tata JR Hammond ML Balkovec JM Einstein M Ge L Harris G Kelly TM Mazur P Pandit S Santoro J Sitlani A Wang C Williamson J Miller DK Yamin TT Thompson CM O'Neill EA Zaller D Forrest MJ Carballo-Jane E Luell S 《Bioorganic & medicinal chemistry letters》2007,17(12):3354-3361
Chemistry was developed to synthesize the title series of compounds. The ability of these novel ligands to bind to the glucocorticoid receptor was investigated. These compounds were also tested in a series of functional assays and some were found to display the profile of a dissociated glucocorticoid. The SAR of the 6,5-bicyclic series differed markedly from the previously reported 6,6-series. Molecular modeling studies were employed to understand the conformational differences between the two series of compounds, which may explain their divergent activity. Two compounds were profiled in vivo and shown to reduce inflammation in a mouse model. An active metabolite is suspected in one case. 相似文献
62.
Zhu-Mei He Michael S Price Gregory R OBrian D Ryan Georgianna Gary A Payne 《BMC microbiology》2007,7(1):104
Background
An available whole genome sequence for Aspergillus flavus provides the opportunity to characterize factors involved in pathogenicity and to elucidate the regulatory networks involved in aflatoxin biosynthesis. Functional analysis of genes within the genome is greatly facilitated by the ability to disrupt or mis-express target genes and then evaluate their result on the phenotype of the fungus. Large-scale functional analysis requires an efficient genetic transformation system and the ability to readily select transformants with altered expression, and usually requires generation of double (or multi) gene deletion strains or the use of prototrophic strains. However, dominant selectable markers, an efficient transformation system and an efficient screening system for transformants in A. flavus are absent. 相似文献63.
BACKGROUND: By 2016, the proportion of Canadians older than 65 years of age will increase to 16%, and there will be an increase in the absolute number of cases of cardiovascular disease in older Canadians. The Canadian Heart Health Surveys database provides information about this population upon which health policy related to cardiovascular disease can be based. This paper presents for the first time population-based data on the risk factors for cardiovascular disease in older Canadians. METHODS: Canadians from all 10 provinces participated in surveys of cardiovascular risk factors; health insurance registries were used as sampling frames. In each province, probability samples of 2200 adults 18 to 74 years old not living in institutions, on reserves or in military camps were asked to participate in interviews and to undergo testing at clinics for major risk factors for cardiovascular disease. RESULTS: A total of 2739 men (response rate 70%) and 2617 women (response rate 66%) aged 55 to 74 years participated in the survey and also provided follow-up clinical measurements at the clinic. Overall, 52% of participants were hypertensive, 26% had isolated systolic hypertension, and 30% had a total blood cholesterol level of 6.2 mmol/L or greater. Rates of current smoking were lower in women than men (17% v. 22%). Overall, 87% of men and 78% of women who were current smokers smoked at least 10 cigarettes per day. Only slightly more than half of participants exercised at least once a week for at least 15 minutes, and almost half had a body mass index of 27 or greater. In only 4% was no major risk factor for cardiovascular disease detected. INTERPRETATION: Significant numbers of older Canadians have one or more major risk factors for cardiovascular disease. Many of these risk factors are amenable to modification. 相似文献
64.
Michael F. Wangler Lawrence T. Reiter Georgianna Zimm Jennifer Trimble-Morgan Jane Wu Ethan Bier 《蛋白质与细胞》2011,2(7):554
Alzheimer’s disease (AD) pathogenesis is characterized by senile plaques in the brain and evidence of oxidative damage. Oxidative stress may precede plaque formation in AD; however, the link between oxidative damage and plaque formation remains unknown. Presenilins are transmembrane proteins in which mutations lead to accelerated plaque formation and early-onset familial Alzheimer’s disease. Presenilins physically interact with two antioxidant enzymes thiol-specific antioxidant (TSA) and proliferation-associated gene (PAG) of the peroxiredoxin family. The functional consequences of these interactions are unclear. In the current study we expressed a presenilin transgene in Drosophila wing and sensory organ precursors of the fly. This caused phenotypes typical of Notch signaling loss-of-function mutations. We found that while expression of TSA or PAG alone produced no phenotype, co-expression of TSA and PAG with presenilin led to an enhanced Notch loss-of-function phenotype. This phenotype was more severe and more penetrant than that caused by the expression of Psn alone. In order to determine whether these phenotypes were indeed affecting Notch signaling, this experiment was performed in a genetic background carrying an activated Notch (Abruptex) allele. The phenotypes were almost completely rescued by this activated Notch allele. These results link peroxiredoxins with the in vivo function of Presenilin, which ultimately connects two key pathogenetic mechanisms in AD, namely, antioxidant activity and plaque formation, and raises the possibility of a role for peroxiredoxin family members in Alzheimer’s pathogenesis. 相似文献
65.
66.
Coevolution of the glucose dehydrogenase gene and the ejaculatory duct in the genus Drosophila 总被引:2,自引:0,他引:2
The glucose dehydrogenase gene (Gld) in Drosophila melanogaster exhibits a
unique spatial and temporal pattern of expression. GLD expression switches
from a non-sex-limited state at the pupal stage to a male-limited state at
the adult stage. At the adult stage, the enzyme is restricted to the
ejaculatory duct. Within the genus Drosophila, the ejaculatory duct has
undergone a simple morphological divergence. In order to determine whether
correlated changes in GLD expression had occurred, GLD activity during the
pupal and adult stages was determined for several Drosophila species. It
was found that virtually all of the species exhibit pupal GLD activity,
whereas only those species with an expanded ejaculatory duct express
male-limited GLD. The results of interspecific genital imaginal disc
transplantation experiments indicate that the expanded morphology and GLD
expression do not require any species- or sex-specific diffusible factors.
An apparent regulatory polymorphism exists within the D. takahashii species
with respect to male-limited GLD expression.
相似文献
67.
68.
DR. Myron A. Mehlman DR. Emil A. Pfitzer DR. Robert A. Scala The Committee to Promote Principles of Reduction Refinement Replacement of Animal Testing in Industrial Toxicology Laboratories 《Cell biology and toxicology》1989,5(3):349-358
The Committee to Promote Principles of Reduction, Refinement and Replacement of Animal Testing in Industrial Toxicology Laboratories was established in 1987 to work toward industrywide improvements in laboratory animal testing methods. The committee's goals are to gather information about effective nonanimal testing techniques and other methods of conserving and improving the care of laboratory animals, to work toward the systematic validation of nonanimal alternatives, and to disseminate useful information about progressive programs and policies throughout the industrial toxicology community. This is the first in a continuing series of reports the committee plans to produce as part of an ongoing program to promote communication among industrial toxicologists about successful methods of reducing, refining and replacing animal testing. Here are some of the report's major findings: (1) Animal care and use committees charged with the oversight of laboratory animal use are a universal practice at the companies surveyed. (2) Significant reductions in the number of animals used for acute toxicity testing have taken place at all the companies during the last 5- to 10-year period. (3) Structure-activity relationships (predicting a test compound's properties based on the known properties of familiar chemicals with similar structures) are widely used to minimize, but not replace, the use of animals. (4) Tissue and organ culture systems are being used with increasing frequency for screening and mechanistic studies, but are not completely replacing animal evaluations as a final step. (5) There is a pressing need for the systematic and scientifically sound validation of nonanimal alternative techniques to reduce the use of animals in toxicology testing while satisfying requirements for the protection of public safety. 相似文献
69.
de Araújo Henriques Ferreira Georgianna Magnani Marciane Cabral Lucélia Brandão Larissa Ramalho Noronha Melline Fontes de Campos Cruz Josiane de Souza Evandro Leite de Brito Alves José Luiz 《Probiotics and antimicrobial proteins》2022,14(2):349-359
Probiotics and Antimicrobial Proteins - High-fat diet (HFD) consumption is a risk factor for dyslipidemias, insulin resistance, and arterial hypertension linked with gut dysbiosis. Probiotic... 相似文献
70.
DR Suresh Vamseedhar Annam K Pratibha BV Maruti Prasad 《Journal of biomedical science》2009,16(1):61-4